Cerebrovascular flow-mediated dilation in humans: Methodological challenges, physiological interpretation and future integrations.

Arterial shear-mediated vasodilation is a well-established measure of endothelial function and serves as a critical biomarker for cardiovascular disease risk. Endothelial function can be measured using a variety of experimental methodologies; however, the most widely adopted technique is ultrasound-based flow-mediated dilation (FMD), in which arterial diameter (e.g., brachial or femoral artery) is quantified before and after a standardized period of blood occlusion using a pressure cuff. Recently, there have been several published studies that have assessed cerebrovascular flow-mediated dilation (cFMD) in the internal carotid artery (ICA) using transient and steady-state hypercapnia. Hypercapnia increases cerebral blood flow (CBF), and the consequent increase in arterial shear stress provokes ICA vasodilation. The ICA diameter response is mediated by endothelial derived nitric oxide, like the peripheral vasculature. Since the introduction of the cFMD technique, there have been several early studies investigating the effects of exercise, environment, autonomic nervous activity, age, sex and vasoactive hormones on cerebral endothelial function. While some findings parallel existing literature on peripheral endothelial function or studies primarily measuring shear stress (e.g. effects of ageing), others reveal unique aspects of cFMD regulation that diverge from trends seen in other techniques (e.g., smoking, sitting and handgrip exercise). This review aims to synthesize early findings on the mechanism(s) underlying cFMD, compare methodological approaches, and outline future research directions and potential clinical applications in this emerging field.